Abstract The freshwater fauna has been judged to be one of the most threatened biotic components in the world. In many tropical‐temperate freshwater habitats worldwide the largest invertebrates are crayfish, as is the case with the cambarid crayfish in Mexico. With 98% of endemic species, most of them with reduced distribution ranges, the Mexican crayfish have not been analysed to examine how diversity, endemism and threat are distributed. A data set was analysed containing 1419 locality records for the 56 species of crayfish occurring in Mexico arranged in a 251 cell grid. Spatial autocorrelation analyses using Moran's I and G* were conducted; species richness, endemism and threat indices were calculated and mapped. An integrated risk score was derived from the two indices. Spatial autocorrelation analyses revealed a pattern that significantly departs from a random arrangement. Moran's I showed a positive autocorrelation between cells that are less than 800 km apart; while G* analysis identified one hotspot of diversity. Four areas with high endemism and seven areas with intermediate endemism values were recognized. The western portion of the Trans‐Mexican Volcanic Belt, and some areas in the north are of special concern owing to the presence of threatened microendemic species. The areas where more threatened species occur differ from those with high endemism values. This distinction makes evident that for species with low dispersal capabilities the areas with high endemism are the product of historical and geological events, while the areas with high numbers of threatened species are those where human activities have had a major impact. The integrated risk score, however, resulting from the combination of endemism and threat, peaks along the Trans‐Mexican Volcanic Belt and where it joins the Sierra Madre Oriental. The integrated risk score proposed in this study, based on well known and frequently used indices in conservation biology, can be used with existing data to determine areas where crayfish species richness, endemism and threat peak to make conservation efforts more cost‐effective. © 2016 The Authors. Aquatic Conservation: Marine and Freshwater Ecosystems published by John Wiley & Sons, Ltd.